Urokinase is a well-known fibrinolytic enzyme. This enzyme has been purified from human urine and human kidney cell culture fluids. Recently, it has also become possible to produce urokinase using recombinant DNA technology (Japanese Patent Application (OPI) No. 60-180591 corresponding to EP-0154272A and U.S. application Ser. No. 703,678 filed Feb. 15, 1985). However, the thus obtained urokinase has a drawback in that when it is used in large doses, degradation and activation of coagulation and fibrinolysis factors occurs which leads to bleeding. On the other hand, it has been found that an inactive-form (precursor) of human urokinase, namely human PUK, produced by human kidney cells (Japanese Patent Application (OPI) No. 60-62981 (corresponding to EP-0139447A and U.S. application Ser. No. 648,134 filed Sept. 7, 1984): J. Biol. Chem., 260, 12377 (1985), unlike Urokinase, dissolves thrombi without inducing any substantial bleeding (Cell Struc. Func., 10, 151 (1985).
Human PUK is composed of three functional domains, i.e., (1) the epidermal growth factor (hereinafter abbreviated as "EGF") domain, the (2) kringle domain and (3) the enzyme activity domain (Hoppe-Seyler's Z., Physiol. Chem., 363, 1155 (1982)).
However, this substance, like urokinase, has a drawback in that it has a short half-life in blood. As a result, relatively large doses are required for the purpose of thrombolysis.